Sequence space

An evolving protein must traverse sequence space.

What determines which paths are accessible?

Epistasis (when a mutations interact with one another) changes the accessibility of evolutionary paths.

Current projects

Can we use the signal from epistasis to dissect the biophysics of these maps?

Can we predict phenotypes given information from a small number of genotypes?


Evolution of innate immune proteins

The innate immune system consists of multiple, interacting parts.

How did each of these parts evolve their functions in innate immunity?

How does calprotectin activate TLR4?

Current projects

What is the mechanism by which calgranulins activate TLR4?

How did the calprotectin heterodimer evolve from an ancestral homodimer?


Evolution of specificity

S100 proteins are small signaling proteins

They bind to metals and downstream peptide regions of protein targets

How did the metal and peptide binding specificity of these target proteins evolve?

Current projects

Define the set of biological targets for S100A5 and S100A6.

What are the chemical "rules" that these low-specificity proteins use to discriminate targets?

Background image: Sunset from Spencer's Butte, 5 miles from the lab.